The following description of the background of the invention is provided simply as an aid in understanding the invention and is not admitted to describe or constitute prior art to the invention.
Leukemia is a malignant disease of the blood-forming organs which involves the distorted proliferation and development of leukocytes and their precursors in bone marrow and blood. Acute myeloid leukemia (AML) is caused by a malignant event occurring in an immature myeloid hematopoietic precursor resulting in cells that proliferate excessively and fail to differentiate normally. In AML patients immature myeloid cells rapidly accumulate and progressively replace the bone marrow leading to diminished production of normal red blood cells, white blood cells and platelets. If untreated, AML patients usually die within months following diagnosis. A form of preleukemia related to AML is known as myelodysplastic syndrome (MDS). MDS encompasses a heterogeneous group of bone marrow disorders characterized by a hypercellular bone marrow with peripheral cytopenia, and propensity to progress to acute myeloid leukemia.
Chronic myloid leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of the capacity to differentiate. Consequently, the peripheral blood cell profile of CML patients shows an increased number of granulocytes and their immature precursors. CML accounts for approximately 20% of all adult leukemias.
The progression of CML disease can be classified into three phases, an initial chronic phase where the disease is often indolent, an accelerated phase (ACC) that may last 6 to 18 months and a blast crisis phase where survival is usually limited to about 3 to 6 months. Before effective treatments were available, CML patients survived on average two years after being diagnosed.
Myeloperoxidase (MPO) is a hallmark enzyme of the myeloid lineage and is found in the granules of myeloid precursors and their leukemic cell counterparts. Determination of the percentage of MPO expressing blast cells has been used as a factor for the diagnosis of AML. A recent publication reported that the percentage of MPO-positive blast cells may be a prognostic factor for AML patients (Matsuo et al., Leukemia, (2003) 17:1538-1543).
Improved methods are needed for diagnosing leukemia and for determining the prognosis of leukemia patients.